Training non-intensivist doctors to work with COVID-19 patients in intensive care units.

BACKGROUND: Due to an expected surge of COVID-19 patients in need of mechanical ventilation, the intensive care capacity was doubled at Rigshospitalet, Copenhagen, in March 2020. This resulted in an urgent need for doctors with competence in working with critically ill COVID-19 patients. A training course and a theoretical test for non-intensivist doctors were developed. The aims of this study were to gather validity evidence for the theoretical test and explore the effects of the course. METHODS: The 1-day course was comprised of theoretical sessions and hands-on training in ventilator use, hemodynamic monitoring, vascular access, and use of personal protective equipment. Validity evidence was gathered for the test by comparing answers from novices and experts in intensive care. Doctors who participated in the course completed the test before (pretest), after (posttest), and again within 8 weeks following the course (retention test). RESULTS: Fifty-four non-intensivist doctors from 15 different specialties with a wide range in clinical experience level completed the course. The test consisted of 23 questions and demonstrated a credible pass-fail standard at 16 points. Mean pretest score was 11.9 (SD 3.0), mean posttest score 20.6 (1.8), and mean retention test score 17.4 (2.2). All doctors passed the posttest. CONCLUSION: Non-intensivist doctors, irrespective of experience level, can acquire relevant knowledge for working in the ICU through a focused 1-day evidence-based course. This knowledge was largely retained as shown by a multiple-choice test supported by validity evidence. The test is available in appendix and online.

Attitudes to drug trials among relatives of unconscious intensive care patients.

BACKGROUND: In many countries relatives are asked to consent on behalf of ICU patients prior to inclusion in clinical trials. However, the attitudes to drug trials among relatives of unconscious ICU patients are largely unknown. METHODS: We performed a prospective questionnaire survey at two university hospital ICUs of the next-of-kin to 50 unconscious adult patients. They were asked to complete a questionnaire within 48 hours of the patients' acute ICU admission. RESULTS: Forty-two relatives returned the questionnaire of which 41 were completed by direct family members and in one case by a friend to the patient.The majority of relatives (36/42) were positive/positive with some scepticism towards performing drug trials in unconscious ICU patients and 30/42 would most likely accept trial-participation by their relative. The majority (30/42) agreed that they should decide if their relative was to participate in a drug trial and 24 of these found that the treating clinician/ICU consultant should also consent. The majority (27/42) found that deferred consent would be acceptable if there was a limited time frame for initiation of treatment, however 8 respondents found this unacceptable when the intervention was a new drug.The majority of relatives stipulated that adherence to legislation, treatment benefit for the study patient and for future patients, no patient-risk or -discomfort and development of new drugs were important factors if their relative was to participate in an ICU drug trial. When questioned about doctors' motives for performing drug trials the wish for drug development and better patient care were highly rated among relatives. CONCLUSIONS: In general, relatives to unconscious ICU patients expressed positive attitudes to drug trials in the ICU and the inclusion of their relative in drug trials. Consent by next-of-kin and deferred consent was acceptable to the majority of relatives.

Offset of pharmacodynamic effects and safety of remifentanil in intensive care unit patients with various degrees of renal impairment.

INTRODUCTION: This open label, multicentre study was conducted to assess the times to offset of the pharmacodynamic effects and the safety of remifentanil in patients with varying degrees of renal impairment requiring intensive care. METHODS: A total of 40 patients, who were aged 18 years or older and had normal/mildly impaired renal function (estimated creatinine clearance >/= 50 ml/min; n = 10) or moderate/severe renal impairment (estimated creatinine clearance <50 ml/min; n = 30), were entered into the study. Remifentanil was infused for up to 72 hours (initial rate 6-9 microgram/kg per hour), with propofol administered if required, to achieve a target Sedation-Agitation Scale score of 2-4, with no or mild pain. RESULTS: There was no evidence of increased offset time with increased duration of exposure to remifentanil in either group. The time to offset of the effects of remifentanil (at 8, 24, 48 and 72 hours during scheduled down-titrations of the infusion) were more variable and were statistically significantly longer in the moderate/severe group than in the normal/mild group at 24 hours and 72 hours. These observed differences were not clinically significant (the difference in mean offset at 72 hours was only 16.5 min). Propofol consumption was lower with the remifentanil based technique than with hypnotic based sedative techniques. There were no statistically significant differences between the renal function groups in the incidence of adverse events, and no deaths were attributable to remifentanil use. CONCLUSION: Remifentanil was well tolerated, and the offset of pharmacodynamic effects was not prolonged either as a result of renal dysfunction or prolonged infusion up to 72 hours.

Plasma YKL-40 and CHI3L1 in systemic inflammation and sepsis-experience from two prospective cohorts.

YKL-40, derived from the CHI3L1 gene, has been associated with outcome of infectious and inflammatory diseases. We hypothesized that plasma YKL-40 concentrations and CHI3L1 genotype could be used as prognostic biomarkers in the assessment of systemic inflammatory response syndrome (SIRS) and sepsis. The objective of the study was to assess the prognostic value of plasma YKL-40 and CHI3L1 genotype in patients with SIRS and sepsis. Plasma YKL-40 and CHI3L1 genotype (rs4950928) were analyzed at time of admission to intensive care units (ICU), in two prospective cohorts of consecutive SIRS patients (cohort 1, n=272; cohort 2, n=502). The plasma YKL-40 cut-off for predicting survival was determined in cohort 1 by receiver operator characteristic analyses and validated in cohort 2. In cohort 1 patients with plasma YKL-40 ≤505ng/ml (area under the curve 0.64 (95% confidence interval (CI) 0.57-0.70), p<0.001, sensitivity 53%, specificity 76%) had superior day 90 survival (81% vs. 55%, p<0.001, hazard ratio (HR) 2.29 (95% CI 1.29-4.07)). In the second cohort plasma YKL-40 ≤505ng/ml was also associated with superior survival (61% vs. 38%, p<0.001, HR 1.43 (1.03-1.99)). CHI3L1 minor allele homozygosity was associated with low plasma YKL-40 at time of admission (p=0.002) and no variation (p=0.462) in concentrations throughout the first 14 days in the ICU, but this was not associated with better survival. In conclusion patients with SIRS and sepsis, plasma YKL-40 ≤505ng/ml at time of ICU admission was associated with better survival. However, this association was not observed for patients homozygous for the low expressing YKL-40 CHI3L1 allele.

Intensive care of haematological patients.

INTRODUCTION: This article presents the treatment results of 320 consecutive patients with malignant haematological diagnoses admitted to a tertiary intensive care unit at a Danish University hospital over a six-year period (2005-2010). With reference to international publications, we describe the development in treatment. MATERIAL AND METHODS: This was a retrospective observational study. RESULTS: The median age was 59 years. The median intensive care unit (ICU) stay was six days. A total of 88% required mechanical ventilation, and 72% received vasopressor treatment. The median Simplified Acute Physiology Score II score was 58. The ICU and one-year mortality rates were 44% and 77%, respectively, but mortality was significantly lower for patients aged 0-20 years. For patients aged 20-80 years, the mortality risk was independent of age. For the group of patients admitted acutely to the ICU with other diagnoses, the ICU- and the one-year mortality rate was 13% and 33%, respectively. CONCLUSION: Despite progress, the mortality rate for haematological patients in ICUs is high. We lack valid tools that allow us to differentiate between those who can benefit from intensive care and those for whom transfer to an ICU is futile. One patient out of five is alive after one year. This supports a strategy offering haematological patients intensive care on an equal footing with other patients. Follow-up studies of survivors, clarification of function level and quality of life are needed. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

[Necrotizing fasciitis]. / Nekrotiserende fasciitis.

INTRODUCTION: Necrotizing fasciitis (NF) is an acute soft-tissue infection, associated with a high mortality and morbidity. To reduce the mortality, an early diagnosis and treatment is essential. Our study aims to identify the number of patients, the microorganisms involved, and NF treatment outcomes among patients admitted to our unit. MATERIAL AND METHODS: This retrospective cohort study enrolled 85 patients admitted to the multidisciplinary, tertiary Intensive Care Unit, Abdominal Center, Rigshospitalet, Denmark in 2005-2007. All received the same protocolled treatment of intensive care, extensive surgical débridements, broad-spectrum antibiotics, intravenous immunoglobulin and hyperbaric oxygen. RESULTS: The microbiological analyses of specimens demonstrated that 51% were positive for polymicrobial infection, 40% for a single pathogen, 74% of these caused by beta-hemolytic streptococci, and 9% of the analyses were inconclusive. Of the patients, 91% required treatment in a respirator, 67.5% presented with septic shock and 25.3% developed acute renal failure needing dialysis. Intensive care unit mortality was 6% and 30-day mortality was 9.5%. Expected mortality based on SAPS II and APACHE II scoring was 38%. Our patients had a significantly higher body mass index than other patients admitted to the unit. CONCLUSION: NF is a complex disease, often associated with multi-organ failure. A protocolled treatment plan with close cooperation between the intensive care, clinical microbiology, medical and surgical specialties seems to reduce mortality considerably in this vulnerable group of patients.

[Prevention of ventilator associated pneumonia in an intensive care unit]. / Forebyggelse af ventilatorassocieret pneumoni på en intensivafdeling.

Important pathogenic mechanisms in ventilator associated pneumonia (VAP) are pharyngeal colonization, micro-aspiration, and exogenously acquired pathogens. Semirecumbent positioning, subglottic suctioning, non-invasive ventilation, oropharyngeal application of chlorhexidine or antibiotics, and selective digestive decontamination (SDD) have all been shown to lower the incidence of VAP. However, regular use of SDD is not recommended in recent guidelines due to the risk of antimicrobial resistance. High hygienic standards and routine surveillance of VAP incidence are mandatory.

Heterozygosity of mannose-binding lectin (MBL2) genotypes predicts advantage (heterosis) in relation to fatal outcome in intensive care patients.

Polymorphisms in the MBL2 gene, which affect the structure and influence on the serum concentration of mannose-binding lectin (MBL), are associated with inflammatory and infectious conditions. The importance of MBL2 polymorphisms on outcome in critical ill patients is unclear. Five hundred and thirty-two consecutive critically ill patients admitted to an intensive care unit (ICU) were included over a period of 18 months. Five hundred and thirty-three individuals served as controls. Vital status was obtained 15.5 months after the last patient was included. MBL2 polymorphisms were determined by a PCR-based assay. Homozygosity for MBL2 variant alleles (O/O) causing MBL structural defects was associated with the highest adjusted mortality rate followed by homozygosity for the normal MBL2 allele (A/A) encoding high MBL levels, whereas heterozygous A/O patients had the most favourable outcome (P = 0.015). MBL2 alleles were not associated with death in ICU (n = 166, P = 0.7), but the association appeared soon after discharge from ICU (n = 366): hazard ratio (HR) for O/O using A/A as reference was 1.33 (95% CI: 0.8-2.2) and for A/O it was 0.62 (95% CI: 0.4-0.8) respectively (P = 0.0045) at completion. No difference in MBL2 frequency was observed between patients and controls at baseline, and between patients classified as having sepsis or not. However, patients with the MBL2 O/O genotype had an increased frequency of Gram-positive bacterial infection (P = 0.01). Heterozygosity for MBL2 alleles confers a protective effect whereas homozygosity is associated with the worst outcome soon after discharge from ICU. This may be an example of heterosis.

[Circulation monitoring of critically ill patients with the Pulse Contour Cardiac Output system]. / Kredsløbsmonitorering af kritisk syge patienter med "pulse contour cardiac output"-systemet.

The Pulse Contour Cardiac Output (PiCCO) monitoring system measures cardiac output with high precision and accuracy. The system may replace the pulmonary artery catheter in most critically ill patients because the rate of serious complications may be lower. Whether the use of dynamic or static fluid monitoring by PiCCO will result in better outcomes should be assessed by studies using clinically relevant end points.

Lung recruitment manoeuvres are effective in regaining lung volume and oxygenation after open endotracheal suctioning in acute respiratory distress syndrome.

INTRODUCTION: Lung collapse is a contributory factor in the hypoxaemia that is observed after open endotracheal suctioning (ETS) in patients with acute lung injury and acute respiratory distress syndrome. Lung recruitment (LR) manoeuvres may be effective in rapidly regaining lung volume and improving oxygenation after ETS. MATERIALS AND METHOD: A prospective, randomized, controlled study was conducted in a 15-bed general intensive care unit at a university hospital. Eight consecutive mechanically ventilated patients with acute lung injury or acute respiratory distress syndrome were included. One of two suctioning procedures was performed in each patient. In the first procedure, ETS was performed followed by LR manoeuvre and reconnection to the ventilator with positive end-expiratory pressure set at 1 cmH2O above the lower inflexion point, and after 60 min another ETS (but without LR manoeuvre) was performed followed by reconnection to the ventilator with similar positive end-expiratory pressure; the second procedure was the same as the first but conducted in reverse order. Before (baseline) and over 25 min following each ETS procedure, partial arterial oxygen tension (PaO2) and end-expiratory lung volume were measured. RESULTS: After ETS, PaO2 decreased by 4.3(0.9-9.7)kPa (median and range; P < 0.005). After LR manoeuvre, PaO2 recovered to baseline. Without LR manoeuvre, PaO2 was reduced (P = 0.05) until 7 min after ETS. With LR manoeuvre end-expiratory lung volume was unchanged after ETS, whereas without LR manoeuvre end-expiratory lung volume was still reduced (approximately 10%) at 5 and 15 min after ETS (P = 0.01). DISCUSSION: A LR manoeuvre immediately following ETS was, as an adjunct to positive end-expiratory pressure, effective in rapidly counteracting the deterioration in PaO2 and lung volume caused by open ETS in ventilator-treated patients with acute lung injury or acute respiratory distress syndrome.